Opposite effects of low and high doses of arginine on glutamate-induced nitric oxide formation in rat substantia nigra

L-arginine is a very versatile amino acid that is involved in many importan t physiological processes such as protein, nitric oxide (NO), agmatine, put rescine, urea, L-ornithine or creatine synthesis and is essential for postt ranslational arginylation of protein. The present study was designed to eva luate in vivo the effect Of L-arginine on NO production in substantia nigra . In vivo spectroscopic and voltammetric studies were addressed in rats to record modifications in methemoglobin and NO levels under glutamate stimula tion. Results showed that, under physiological L-arginine extracellular con centration, the intranigral infusion of glutamate produced an increase in N O levels. When a low dose Of L-arginine was co-Infused with glutamate, a pe rsistent and higher increase in NO levels was observed. The co-infusion of glutamate with a moderate dose Of L-arginine induced drastic and persistent NO production. It was also observed that high doses of either L-arginine o r D-arginine inhibit NO production. Subsequently, these data show that L-ar ginine and D-arginine are involved in a mechanism that inhibits NO producti on. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.